Splenic extramedullary hematopoietic proliferation in Philadelphia chromosome-negative myeloproliferative neoplasms: heterogeneous morphology and cytological composition

We studied 24 spleens with extramedullary hematopoietic proliferation (EMHP), a key feature of advanced-stage Philadelphia chromosome-negative myeloproliferative neoplasms, obtained from 24 patients (14 primary myelofibrosis, 7 polycythemia vera and 3 unclassifiable). Hematoxylin and eosin, reticulin and trichrome stains, and immunohistochemical stains for myeloperoxidase, glycophorin-C, CD42b, CD34, CD117, CD8, nerve growth factor receptor and smooth muscle actin were evaluated. Clinical information was correlated with the morphological findings. Three distinct histological patterns of EMHP were recognized: diffuse (12), nodular (5), and mixed-nodular and diffuse (7). The preponderant lineage was granulocytic in diffuse, trilineage in nodular and erythroid in mixed EMHP. Erythropoiesis was largely intravascular, granulopoiesis was within the splenic cords and megakaryopoiesis was observed in both locations. The stromal changes paralleled the histological pattern with preservation of the splenic stromal and vascular architecture in the diffuse areas as opposed to areas of nodular EMHP. The morphological features of the splenic EMHP did not correlate with specific subtypes of myeloproliferative neoplasms. The mean duration of follow-up from initial diagnosis was 80 months. A total of 15 of the 24 patients died of disease: 8 of 12 (67%) with diffuse, 2 of 5 (40%) with nodular and 5 of 7 (71%) with mixed growth patterns. The mean duration from diagnosis to splenectomy was shorter in patients with diffuse (83 months) as compared with those with nodular EMHP (127 months). Our study demonstrates that splenic extramedullary hematopoietic proliferation in Philadelphia chromosome-negative myeloproliferative neoplasms shows distinct histological patterns that do not correlate with disease subtypes, but appear to suggest a trend between the histological patterns and clinical behavior. These results suggest a different biology of the disease in the nodular and diffuse extramedullary hematopoietic proliferation groups.     

A plant based protective antigen [PA(dIV)] vaccine expressed in chloroplasts demonstrates protective immunity in mice against anthrax

The currently available anthrax vaccines are limited by being incompletely characterized, potentially reactogenic and have an expanded dosage schedule. Plant based vaccines offer safe alternative for vaccine production. In the present study, we expressed domain IV of Bacillus anthracis protective antigen gene [PA(dIV)] in planta (by nuclear agrobacterium and chloroplast transformation) and E. coli [rPA(dIV)]. The presence of transgene and the expression of PA(dIV) in planta was confirmed by molecular analysis. Expression levels up to 5.3% of total soluble protein (TSP) were obtained with AT rich (71.8% AT content) PA(dIV) gene in transplastomic plants while 0.8% of TSP was obtained in nuclear transformants. Further, we investigated the protective response of plant and E. coli derived PA(dIV) in mice by intraperitoneal (i.p.) and oral immunizations with or without adjuvant. Antibody titers of >10⁴ were induced upon i.p. and oral immunizations with plant derived PA(dIV) and oral immunization with E. coli derived PA(dIV). Intraperitoneal injections with adjuvanted E. coli derived PA(dIV), generated highest antibody titers of >10⁵. All the immunized groups demonstrated predominant IgG1 titers over IgG2a indicating a polarized Th2 type response. We also evaluated the mucosal antibody response in orally immunized groups. When fecal extracts were analyzed, low sIgA titer was demonstrated in adjuvanted plant and E. coli derived PA(dIV) groups. Further, PA(dIV) antisera enhanced B. anthracis spore uptake by macrophages in vitro and also demonstrated an anti-germinating effect suggesting a potent role at mucosal surfaces. The antibodies from various groups were efficient in neutralizing the lethal toxin in vitro. When mice were challenged with B. anthracis, mice immunized with adjuvanted plant PA(dIV) imparted 60% and 40% protection while E. coli derived PA(dIV) conferred 100% and 80% protection upon i.p. and oral immunizations. Thus, our study is the first attempt in highlighting the efficacy of plant expressed PA(dIV) by oral immunization in murine model.     

Social, economic and legal dimensions of tobacco and its control in South-East Asia region

This paper examines the social, cultural, economic and legal dimensions of tobacco control in the South-East Asia Region in a holistic view through the review of findings from various studies on prevalence, tobacco economics, poverty alleviation, women and tobacco and tobacco control laws and regulations. Methods were Literature review of peer reviewed publications, country reports, WHO publications, and reports of national and international meetings on tobacco and findings from national level surveys and studies. Tobacco use has been a social and cultural part of the people of South-East Asia Region. Survey findings show that 30% to 60% of men and 1.8% to 15.6% of women in the Region use one or the other forms of tobacco products. The complex nature of tobacco use with both smoking and smokeless forms is a major challenge for implementing tobacco control measures. Prevalence of tobacco use is high among the poor and the illiterate. It is higher among males than females but studies show a rising trend among girls and women due to intensive marketing of tobacco products by the tobacco industry. Tobacco users spend a huge percent of their income on tobacco which deprives them and their families of proper nutrition, good education and health care. Some studies of the Region show that cost of treatment of diseases attributable to tobacco use was more than double the revenue that governments received from tobacco taxation. Another challenge the Region faces is the application of uniform tax to all forms of tobacco, which will reduce not only the availability of tobacco products in the market but also control people switching over to cheaper tobacco products. Ten out of eleven countries are Parties to the WHO Framework Convention on Tobacco Control and nine countries have tobacco control legislation. Enforcement of control measures is weak, particularly in areas such as smoke-free environments, advertisement at the point of sale and sale of tobacco to minors. Socio-cultural acceptance of tobacco use is still a major challenge in tobacco control efforts for the governments and stakeholders in the South-East Asia Region. The myth that chewing tobacco is less harmful than smoking tobacco needs to be addressed with public awareness campaigns. Advocacy on the integration of tobacco control with poverty alleviation campaigns and development programs is urgently required. Law enforcement is a critical area to be strengthened and supported by WHO and the civil society organizations working in the area of tobacco control.